Protein Kinase A at the Centrosome
Protein kinase A regulatory subunit RIIalpha (PKA-RIIa) is tightly bound to centrosomal structures during interphase through interaction with the A-kinase anchoring protein AKAP350 (also known as AKAP450 and CGNAP), MAP2 and Pericentrin. This diagram illustrates these three PKA-RII binding complexes. The cyclin B-p34(cdc2) kinase (CDK1) has been shown to phosphorylate PKA-RIIa on T54 and this has been proposed to alter the subcellular localization of PKA-RIIa at the on set of mitosis. It has been demonstrated that PKA-RIIa dissociates and redistributes from centrosomes at mitosis. The focal point of this illustration is the AKAP350 complex. In addition to binding PKA-RIIa, AKAP350 binds PKN (Takahashi et al 1999) and the phosphatases PP1 and PPA2 (Takahashi et al 1999). PKN is a serine/threonine protein kinase, having a catalytic domain homologous to the PKC family in the C-terminal region and a unique regulatory region in the N-terminal region. PKN is activated by a small GTPase RhoA and unsaturated fatty acids such as arachidonic acid. The binding of both kinases and phophatases by the same scaffold protein provides a focal point where physiological events, such as cell cycle progression and intracellular membrane traffic, may be regulated by phosphorylation state of specific protein substrates. There are at least 4 isoforms of AKAP350 which lead to the possibility that they may behave differently at different subcellular locations. MAP2 is a member of a group of proteins that provide microtubule stabilization. MAP2 affinity appears to be dependent on PKA phosphorylation of MAP2. Pericentrin is also an AKAP (Diviani and Scott). Pericentrin binds Dynein which is also regulated by PKA leading to the possibility that pericentrin positions PKA to regulate dynein function (Diviani and Scott). Another example of AKAP/PKA interaction is illustrated in the AKAP95 role in mitosis and chromosome dynamics” pathway.
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REFERENCES: Carlson CR, Witczak O, Vossebein L, Labbe JC, Skalhegg BS, Keryer G, Herberg FW, Collas P, Tasken K. CDK1-mediated phosphorylation of the RIIalpha regulatory subunit of PKA works as a molecular switch that promotes dissociation of RIIalpha from centrosomes at mitosis. J Cell Sci. 2001 Sep;114(Pt 18):3243-54. Diviani D, Scott JD. AKAP signaling complexes at the cytoskeleton. J Cell Sci. 2001 Apr;114(Pt 8):1431-7.
